The present invention relates generally to the field of molecular medicine and more specifically to methods of identifying a preferred liver transplant donor.
Chronic hepatitis C virus (HCV) infection afflicts an estimated 4 to 4.5 million Americans. HCV infection contributes to the deaths of more than 12,000 Americans every year and is a principal cause of chronic liver disease, cirrhosis, and liver cancer. Liver failure due to hepatitis C infection is the leading cause of liver transplants in the U.S.
Even though acute hepatitis C, at first, is largely asymptomatic, a flu-like illness is often mentioned by patients who are later diagnosed with the disease. About nine out of ten people who contract an acute infection of HCV will go on to develop chronic hepatitis, characterized by extreme fatigue, depression, fever, mood changes, and weakness. Of those who eventually develop chronic hepatitis C, a large number will develop cirrhosis, portal hypertension, and liver failure, some in as few as 10 years, and some will require a liver transplant. Hepatitis C is a silent killer because both the acute and chronic phases of the disease usually produce no specific symptoms. The acute phase is identified only if there is a definite recent risk factor such as a needle stick, surgery or a tattoo. Modes of transmission include body piercing, oral surgery, dialysis, acupuncture, vaccinations, and tainted blood products.
The chronic form of hepatitis C can persist for decades without any outward signs or symptoms of the disease while some patients are developing irreversible cirrhosis and possibly liver cancer. There is no cure or vaccine for hepatitis C, although a single treatment, alpha interferon, is available. Unfortunately, only about 15 percent of hepatitis C patients who take alpha interferon will go into remission.
During the next decade, the U.S. healthcare system could be overwhelmed by hepatitis C virus-related liver diseases, as deaths double and the need for liver transplants increase five-fold. The 20-year outlook is even more daunting, with HCV-related deaths projected to almost quadruple by 2018 and the demand for liver transplants expected to be eight times higher than today. It is estimated that the demand for orthotopic liver transplantation (OLT) will increase 5- to 7-fold in the next 10 to 20 years.
Unfortunately, following liver transplantation in a HCV infected patient, reinfection of the transplanted liver with HCV invariably occurs. Although an association between HCV infection and TNF-α expression has been previously described (Larrea et al., Hepatology 23:210-217 (1996)), no previous studies have investigated any possible contribution of the liver donor to TNF-α expression and the recurrence of hepatitis C in a liver transplant recipient. Because the rate, frequency and severity of hepatitis C recurrence after liver tranplantation varies with different patients, there exists a need to identify a preferred liver transplant donor whose transplanted liver would limit the severity of recurrence of hepatitis C. The present invention satisfies this need and provides related advantages as well.